Diabetes Research: Advancing Toward a Cure

George L. King, M.D.Research Director and Head of the Section on Vascular Cell Biology,Joslin Diabetes Center; Professor of Medicine, Harvard Medical School

This is an incredibly exciting time in diabetes research. In the past, we only have had one promising approach to finding a cure for patients with type 1 diabetes. Now we have several possibilities related to a cure, and even prevention, both for type 1 and type 2 diabetes.

Previously, research toward a cure was focused on transplantation of the cells in the pancreas that produce insulin, the islet cells or parts of the pancreas. In type 1 diabetes, the body’s immune system turns on itself and destroys these islet cells. As a result, the body can’t produce the insulin required to escort glucose from the food we eat to where it is needed—into the cells of the body’s muscles and other organs. We are now focusing on ways to understand this immune attack to find safe ways to block it. There are several ongoing studies using our knowledge of immunology to try to intervene and prevent type 1 diabetes.

Another important effort is directed to regenerating islet cells—to produce insulin again—either through the use of stem cells, embryonic or adult, or other ways of engineering these cells. We are now hopeful that a large number of people with type 1 diabetes still have surviving islet cells left to regrow. This optimism has been raised by the findings that many type 1 diabetes patients may still have residual islets that have retained some function to make insulin. A recent Joslin study of people who have lived more than 50 years with type 1 diabetes indicated that even some of these patients can still make insulin.

Much attention is also aimed at the causes of type 2 diabetes. The main theory involves inflammation. Joslin researchers have pursued this idea from the basic science level, now resulting in a multi-center clinical trial of humans taking anti-inflammatory drugs to see if these drugs will decrease the incidence of type 2 diabetes.

In addition, diabetes investigators are working on understanding how islet cells malfunction in type 2 diabetes. What is the genetic basis for this? Why can islets in some people continue to compensate by making more and more insulin for many years without getting diabetes, whereas others can’t keep up with the increased demand? Our goal is to improve the compensation mechanism to prevent type 2 diabetes, and Joslin investigators are now clinically testing ways to do this.

Progress in Preventing Complications

There have also been breakthroughs in understanding and preventing diabetes complications. Many years of high glucose levels can damage blood vessels and nerves in the eyes, kidneys and other organs throughout the body.

Research that I have pursued for 25 years, for example, has led to the development of a potential new drug. The new drug, called ruboxistaurin (RBX), reduces the occurrence of moderate vision loss due to diabetes, and also looks promising for treating diabetic kidney disease and possibly heart disease. This drug evolved from a discovery: Joslin scientists uncovered a major signaling pathway at the molecular level by which high amounts of glucose damage blood vessels. RBX blocks a form of an enzyme that the Joslin team found is activated in blood vessels in eyes, kidney and the heart.

Diabetes affects so many different parts of the body. To find solutions, we must bring together different types of experts so problems can be attacked from various angles. For example, cardiovascular disease is a significant complication of diabetes that has to be tackled from several perspectives. Genetics researchers concentrate on the genetic changes of people with diabetes that make them vulnerable to cardiovascular problems, such as heart attacks and stroke. Other scientists focus on the impact of insulin on the blood vessels and how this relates to cardiovascular problems. Finally, researchers who specialize in metabolism study the significance of exercise on improving the use of glucose through the body, which might also have an effect in preventing cardiovascular disease.

Diabetes researchers are making great progress in understanding the basic science of diabetes. Many findings have already proceeded on the road to new treatments. For every new strategy that succeeds, the benefit to millions of people will be huge.

This article originally appeared in the Special Diabetes Insert in the Nov. 13, 2006 issue of TIME Magazine.